猪树突状细胞CD205纳米抗体介导FMDV抗原靶向提呈及其效应机制

猪口蹄疫（FMD）疫苗在口蹄疫防控中发挥着重要作用，但仍存在抗原用量较大、不能诱导有效的细胞免疫等不足。CD205作为树突状细胞（DC）特异性的抗原提呈受体，抗原经CD205靶向后，可以诱导高效的免疫应答，在抗病毒感染和肿瘤治疗方面展现了良好的应用前景。CD205靶向在兽医领域研究日益受到关注，但其效应机制尚不清楚。本研究通过构建猪CD205/FMDV双特异纳米抗体实现FMDV抗原的CD205靶向，分别进行体内试验与体外试验，结合对抗原的不同处理，阐明CD205介导FMDV抗原靶向提呈的动力学过程、DC活化成熟、体液免疫及细胞免疫效应，并结合对DC蛋白质代谢的不同抑制剂处理以及CD4+T细胞、CD8+T细胞阻断试验，解析CD205介导FMDV抗原靶向提呈的效应机制。本研究不仅有助于设计针对猪CD205的新型、高效、主动靶向抗原输送系统，而且将对新型FMD疫苗设计提供思路和参考。

Pig foot-and-mouth disease vaccine plays an important role in the prevention and control of foot-and-mouth disease, but still has some shortcomings, such as large amount of antigen and inability to induce effective cellular immunity. CD205 is a specific antigen presenting molecule of dendritic cells, efficient immunity could be improved by targeting to CD205, which had a good application prospect during antiviral infection and oncotherapy. CD205 targeting has attracted increasing attention in the field of veterinary research, while its effect mechanism was still unclear. In this study, CD205 targeting of FMDV antigen was achieved by constructing a anti-pig CD205/FMDV bispecific-nanobody. In vitro and in vivo experiments were carried out, respectively, the dynamic process of CD205-mediated FMDV antigen targeting presentation, DC activation and maturation, humoral immunity and cellular immunity effects were clarified combined with different treatment of antigen. The mechanism of CD205-mediated FMDV antigen targeting presentation was analyzed in combination with different inhibitor treatments of DC protein metabolism and CD4+T cell and CD8+T cell blocking tests. This study would not only contribute to the design of a novel, efficient and actively antigen targeted delivery system for pig CD205, but also provide ideas and references for the design of novel FMD vaccines.